Curcumin and Nano-Curcumin Mitigate Copper Neurotoxicity by Modulating Oxidative Stress, Inflammation, and Akt/GSK-3β Signaling

Abstract

Copper (Cu) is essential for multiple biochemical processes, and copper sulphate (CuSO4) is a pesticide used for repelling pests. Accidental or intentional intoxication can induce multiorgan toxicity and could be fatal. Curcumin (CUR) is a potent antioxidant, but its poor systemic bioavailability is the main drawback in its therapeutic uses. This study investigated the protective effect of CUR and N-CUR on CuSO4-induced cerebral oxidative stress, inflammation, and apoptosis in rats, pointing to the possible involvement of Akt/GSK-3β. Rats received 100 mg/kg CuSO4 and were concurrently treated with CUR or N-CUR for 7 days. Cu-administered rats exhibited a remarkable increase in cerebral malondialdehyde (MDA), NF-κB p65, TNF-α, and IL-6 associated with decreased GSH, SOD, and catalase. Cu provoked DNA fragmentation, upregulated BAX, caspase-3, and p53, and decreased BCL-2 in the brain of rats. N-CUR and CUR ameliorated MDA, NF-κB p65, and pro-inflammatory cytokines, downregulated pro-apoptotic genes, upregulated BCL-2, and enhanced antioxidants and DNA integrity. In addition, both N-CUR and CUR increased AKT Ser473 and GSK-3β Ser9 phosphorylation in the brain of Cu-administered rats. In conclusion, N-CUR and CUR prevent Cu neurotoxicity by attenuating oxidative injury, inflammatory response, and apoptosis and upregulating AKT/GSK-3β signaling. The neuroprotective effect of N-CUR was more potent than CUR.

Nano-Curcumin Prevents Copper Reproductive Toxicity by Attenuating Oxidative Stress and Inflammation and Improving Nrf2/HO-1 Signaling and Pituitary-Gonadal Axis in Male Rats

“…Oxidative stress has been suggested to play a key role in Cu toxicity [ 15 , 16 ], and some researchers have demonstrated that its testicular toxicity occurs via provoking oxidative damage [ 19 , 24 ]. Cu is able to cycle easily between unstable reduced and stable oxidized states and facilitate redox reactions.…”

“…Inflammation and apoptosis are implicated in the toxic effects of Cu, including neurotoxicity [ 15 ], cardiotoxicity [ 16 ] and testicular toxicity [ 24 ]. Here, NF-κB, iNOS, and TNF-α were significantly upregulated in the testes of rats that received CuSO 4 , denoting an inflammatory response.…”

“…Accordingly, exposure of rats to CuSO 4 resulted in increased Cu levels in the liver and kidney and subsequently impairment and damage of these organs [ 14 ]. Recent work from our lab has demonstrated neurotoxicity and cardiac injury in rats exposed to CuSO 4 [ 15 , 16 ].…”

Heavy Metal Accumulation, Tissue Injury, Oxidative Stress, and Inflammation in Dromedary Camels Living near Petroleum Industry Sites in Saudi Arabia

“…Some HMs function as micronutrients and are involved in vital metabolic and cellular processes; however, they are toxic beyond their physiological concentrations [20]. The toxic effects of HMs have been demonstrated in numerous studies [21][22][23][24], with neurotoxicity, cancer, hepatotoxicity, reproductive toxicity, cancer, osteoporosis, and other disorders among the effects of chronic exposure to HMs [17,[25][26][27][28][29]. Increased production of reactive oxygen species (ROS) and oxidative injury have been implicated in the toxicity of HMs [30,31].…”

The Multifaceted Role of Curcumin in Advanced Nanocurcumin Form in the Treatment and Management of Chronic Disorders

“…W.S. Sarawi et al [ 44 ] examined the impact of curcumin and nanocurcumin on copper sulphate (CuSO 4 )-induced brain oxidative stress, inflammation, and apoptosis in rats, and found that Akt/GSK-Akt/GSK-3β may be involved. Rats were given 100 mg/kg CuSO4 and were also given curcumin and nanocurcumin for 7 days.…”